**3. Epidemiology and risk factors**

#### **3.1. Prevalence**

and affect activities of daily living. The disease is a clinical diagnosis and only requires further testing to exclude other pathologies. There is no cure for Dupuytren's disease and treatment methods remain palliative. Patients with mild disease can be observed for disease progression while patients with more severe disease may be treated with a variety of procedures or surgeries. Recently, clinical procedures including collagenase injections and percutaneous needle fasciotomy (PNF) have been utilized to successfully treat select patients. Still, surgery remains the preferred method of treating Dupuytren's contractures for most surgeons. A variety of surgical techniques have been described utilizing different types of incisions to either incise or excise disease fascia and correct contractures. Surgery has yielded successful outcomes in regaining extension of the involved digits and improving function of the hand, however, it is not without risks. Complications related to infection, wound healing, and neurovascular injuries have been reported. In addition, despite successful treatment following surgery some patients experience recurrence of their contracture. Further research has focused on methods of successfully treating Dupuytren's disease while reducing complications and recurrence. This chapter will provide a thorough description of Dupuytren disease from its history and pathophysiology to

clinical management as well as highlight research related to patient outcomes.

America, and is now found throughout the world.

Dupuytren's disease is a condition of the hand with a unique history. Its origin is linked to the Viking population and likely spread throughout Northern Europe as the Vikings conquered and acquired lands in the ninth through thirteenth century. For this reason, it has since been given the colloquial name, "Viking disease." The Viking's 300-year conquest lead to many settlements in which their descendants lived and bred with native populations, leading to the spread of Dupuytren's disease to many northern European nationalities [1, 2]. Naturally, as time progressed and more conquests occurred, the disease spread to the shores of North

Early evidence of diseases mimicking Dupuytren's has been noted in historical texts. The "Curse of the MacCrimmons" is a tale of seventeenth century Scotland in which Clan MacCrimmons was cursed with a "bent finger," leaving them unable to play their bagpipes [2, 3]. The Catholic Church sign of benediction has even been postulated to depict an early church priest with Dupuytren's disease [2, 4]. Whaley and Elliot describe early Icelandic stories of the twelfth and thirteenth century possibly describing accounts of Dupuytren's disease dating back to the ninth century and include the treatment of one case by a procedure resembling a palmar

In 1831, the French surgeon and namesake to the disease Baron Guillaume Dupuytren gave a lecture on the "permanent retractions of the flexed fingers" [6]. Other surgeons have also been credited with describing conditions believed to be caused by Dupuytren's disease, including: Felix Platter in 1680, Henry Cline, Jr. in 1808, and Sir Astley Cooper in 1818 [2]. Elliot discusses a "Cline's contracture" as an earlier description of Dupuytren's disease [7]. MacFarlane reports Platter may have been the first to publish a description of Dupuytren's disease as early

**2. History**

58 Essentials of Hand Surgery

fasciotomy [5].

Dupuytren's disease is most prominent in Northern European white males, especially greater than 40 years old. A study in the Netherlands reports a prevalence as high as 22% in the general population [11]. The study also demonstrated a propensity for older populations with ages 50–55 displaying a 4.9% prevalence, while those 76–80 years old having a prevalence of 52.6%. Men were also affected disproportionately more than women (26.4 vs. 18.6%). The prevalence in the US has been shown to approach 7.3% when including self-reported symptoms [12]. Other epidemiological studies show a male to female ratio in the US of 1.7:1 which approaches 1:1 with increasing age [13]. Dupuytren's disease has been linked to both genetic and environmental factors, both of which contribute to the prevalence in patient populations throughout the world.

#### **3.2. Genetics**

The genetic component of Dupuytren's disease has been a topic of interest for many years. A study by Burge et al. found that the prevalence of Dupuytren's in Norwegian individuals over 60 years old reaches 30%, indicating a familial component in like populations [14]. They also suggested an autosomal dominant inheritance pattern with variable penetrance based on pedigree analysis. Multiple heritable patterns have been hypothesized, but there is no clear consensus on a mode of transmission. It is possible the disease does not carry a simple inheritance pattern, but rather follows a more complex method similar to heart disease and diabetes. Ling et al. performed a study examining the family members of patients with Dupuytren's disease, and found that 53% of men and 33% of women over the age of 60 in the family had signs of the disease [15]. In a clinical study, patients with a family history of Dupuytren's disease had a 6-year earlier onset of disease compared to patients without a family history [16]. There was also increased disease severity in terms of the number of affected digits and degree of contracture in patients with a family history. Both of these findings suggest patients with a family history of Dupuytren's disease develop a more severe and earlier onset of disease. Research has also investigated specific genes linked to the development of Dupuytren's, including the gene for TGF-β1. However, studies implicating TGF- β1 with Dupuytren's disease have been inconclusive [17]. The genetic predisposition of Dupuytren's disease is complex and further research is needed to elicit a clear relationship between genetics and disease manifestation.

Dupuytren's disease in adult diabetics and suggested Dupuytren's severity is usually more mild and affecting the middle finger in diabetics [23]. In addition, 13% of 134 patients with Dupuytren's disease were found to have elevated glucose levels, suggesting elevated blood glucose levels may influence development of Dupuytren's disease. In another study, the proportion of German diabetics with Dupuytren's disease was only slightly higher than that of the normal population (11% compared to about 7%) [24]. Another study however, showed the prevalence of the disease in diabetic patients was as high as 32% [25]. Though the prevalence of DD in diabetics has been studied in various subpopulations, a consensus on the relationship between Dupuytren's disease and diabetes mellitus has not been reached. Further research is needed to demonstrate a true mechanism of pathogenesis between Dupuytren's

Dupuytren's Disease

61

http://dx.doi.org/10.5772/intechopen.72759

Dupuytren himself first proposed previous trauma as a risk factor for developing the disease [26]. The progression of Dupuytren's disease resembles normal physiologic healing and based on a patient's risk factors, trauma may initiate a cascade of events leading to an aberrant healing response. It is unclear whether the development of disease is related to a single injury or rather multiple insults over time, but studies have reported the development of Dupuytren's near the site of previous penetrating injuries [27]. Other studies have linked previous hand surgery such as carpal tunnel and trigger finger release to the development of

The association between Dupuytren's disease and epilepsy or anticonvulsants and has been reported. Lund et al. recorded a 50% prevalence of Dupuytren's in male patients with epilepsy and 25% in females [30]. Another study identified an overall prevalence of Dupuytren's disease in 37% of epileptics [31]. Critchley et al. reported a 56% incidence of Dupuytren's disease in chronic epileptic patients and an associated increased in disease with duration of epilepsy and possibly related to the administration of the anticonvulsant phenobarbital [32]. The effect of phenobarbital on DD was analyzed in a 2011 study, in which a dose-dependent fibrotic effect was seen with phenobarbital use. Though these studies demonstrate a relationship between epilepsy and phenobarbital use in DD, other studies have found no direct cor-

Manuel labor consisting of continued and repetitive hand use has also been proposed as a risk factor for developing Dupuytren's disease. Lucas et al. reported the effect of personal and occupation exposures on the development of the disease and reported men who developed the disease had the highest exposure to biomechanical, vibration, and manual work [35]. After adjusting for personal risk factors, manual labor and the handling of vibratory tools had the strongest association with Dupuytren's disease. Another study examining the effect of weekly hand transmitted vibration on the development of Dupuytren's disease concluded the risk of developing Dupuytren's contracture is more than double in men with increasing amounts of hand-transmitted vibration [34]. In addition, handwork for at least 30 years has also been reported as a possible risk factor in the development of Dupuytren's disease [35].

disease and diabetes.

*3.3.5. Other risk factors*

Dupuytren's disease [22, 25, 28, 29].

relation to antiepileptic drugs [33, 34].

*3.3.4. Trauma*

#### **3.3. Environmental factors**

Despite Dupuytren's genetic tendencies, multiple patients with no familial history of the disease are affected every year. Certain environmental factors have been associated with the development of Dupuytren's disease including smoking, alcohol use, diabetes, manual labor, and previous trauma. Hindocha et al. identified additional risk factors in developing Dupuytren's and included frozen shoulder, epilepsy, and a high lipid profile [16]. There are many environmental risk factors associated with Dupuytren's disease; however, smoking, alcohol, diabetes mellitus, and previous trauma are the most well-established factors cited in current literature.

#### *3.3.1. Smoking*

There is a high prevalence of patients with Dupuytren's disease who smoke cigarettes. A study found 76.5% of Dupuytren's patients were smokers, while only 37.2% of the control group were smokers [18]. Another study examined 222 patients undergoing surgery to treat a Dupuytren's contracture and found smoking was strongly associated with Dupuytren's requiring surgical intervention (OR 2.8, 95% CI 1.5–5.2) [19]. The pathogenesis of Dupuytren's disease from smoking is likely related to its impact on circulation. Cigarette smoking affects the small blood vessels causing microangiopathies, resulting in reduced blood flow to the distal extremities including the hands. The microvascular impairment from smoking is believed to contribute to the development of the Dupuytren's disease. Smoking induced hypoxia of distal extremities leads to PDGF release, triggering endothelial and fibroblast activation resulting in increased collagen synthesis [8]. These vascular changes associated with smoking and collagen synthesis may contribute to the pathogenesis of Dupuytren's. Overall, smoking is a modifiable risk factor that likely increases one's risk of developing Dupuytren's disease.

#### *3.3.2. Alcohol*

Though the role of alcohol is not clearly identified, it has been shown to be a risk factor for the development of Dupuytren's disease. One study suggested alcoholic consumption leads to impaired liver function, and in turn altered palmar fat composition which could as a trigger for developing Dupuytren's [20]. Heavy drinking was found to be more common in a study of Dupuytren's patients awaiting surgery, and another study reported alcohol was the second most important risk factor after age in developing the disease [20, 21]. Additional studies suggest that alcoholics have a higher prevalence of Dupuytren's disease compared to non-alcoholics (28 vs. 22%, respectively) [22]. Though associations have been documented, further research is needed in identifying the role of alcohol as a modifiable risk factor for developing Dupuytren's disease.

#### *3.3.3. Diabetes mellitus*

Multiple studies have identified a relationship between Dupuytren's disease and diabetes, but there is no clear evidence its pathophysiology. Noble et al. reported a 42% incidence of Dupuytren's disease in adult diabetics and suggested Dupuytren's severity is usually more mild and affecting the middle finger in diabetics [23]. In addition, 13% of 134 patients with Dupuytren's disease were found to have elevated glucose levels, suggesting elevated blood glucose levels may influence development of Dupuytren's disease. In another study, the proportion of German diabetics with Dupuytren's disease was only slightly higher than that of the normal population (11% compared to about 7%) [24]. Another study however, showed the prevalence of the disease in diabetic patients was as high as 32% [25]. Though the prevalence of DD in diabetics has been studied in various subpopulations, a consensus on the relationship between Dupuytren's disease and diabetes mellitus has not been reached. Further research is needed to demonstrate a true mechanism of pathogenesis between Dupuytren's disease and diabetes.

#### *3.3.4. Trauma*

Dupuytren's disease have been inconclusive [17]. The genetic predisposition of Dupuytren's disease is complex and further research is needed to elicit a clear relationship between genet-

Despite Dupuytren's genetic tendencies, multiple patients with no familial history of the disease are affected every year. Certain environmental factors have been associated with the development of Dupuytren's disease including smoking, alcohol use, diabetes, manual labor, and previous trauma. Hindocha et al. identified additional risk factors in developing Dupuytren's and included frozen shoulder, epilepsy, and a high lipid profile [16]. There are many environmental risk factors associated with Dupuytren's disease; however, smoking, alcohol, diabetes mellitus, and previous trauma are the most well-established factors cited in current literature.

There is a high prevalence of patients with Dupuytren's disease who smoke cigarettes. A study found 76.5% of Dupuytren's patients were smokers, while only 37.2% of the control group were smokers [18]. Another study examined 222 patients undergoing surgery to treat a Dupuytren's contracture and found smoking was strongly associated with Dupuytren's requiring surgical intervention (OR 2.8, 95% CI 1.5–5.2) [19]. The pathogenesis of Dupuytren's disease from smoking is likely related to its impact on circulation. Cigarette smoking affects the small blood vessels causing microangiopathies, resulting in reduced blood flow to the distal extremities including the hands. The microvascular impairment from smoking is believed to contribute to the development of the Dupuytren's disease. Smoking induced hypoxia of distal extremities leads to PDGF release, triggering endothelial and fibroblast activation resulting in increased collagen synthesis [8]. These vascular changes associated with smoking and collagen synthesis may contribute to the pathogenesis of Dupuytren's. Overall, smoking is a modifiable risk factor that likely increases one's risk of developing Dupuytren's disease.

Though the role of alcohol is not clearly identified, it has been shown to be a risk factor for the development of Dupuytren's disease. One study suggested alcoholic consumption leads to impaired liver function, and in turn altered palmar fat composition which could as a trigger for developing Dupuytren's [20]. Heavy drinking was found to be more common in a study of Dupuytren's patients awaiting surgery, and another study reported alcohol was the second most important risk factor after age in developing the disease [20, 21]. Additional studies suggest that alcoholics have a higher prevalence of Dupuytren's disease compared to non-alcoholics (28 vs. 22%, respectively) [22]. Though associations have been documented, further research is needed in identifying the role of alcohol as a modifiable risk factor for developing Dupuytren's disease.

Multiple studies have identified a relationship between Dupuytren's disease and diabetes, but there is no clear evidence its pathophysiology. Noble et al. reported a 42% incidence of

ics and disease manifestation.

**3.3. Environmental factors**

60 Essentials of Hand Surgery

*3.3.1. Smoking*

*3.3.2. Alcohol*

*3.3.3. Diabetes mellitus*

Dupuytren himself first proposed previous trauma as a risk factor for developing the disease [26]. The progression of Dupuytren's disease resembles normal physiologic healing and based on a patient's risk factors, trauma may initiate a cascade of events leading to an aberrant healing response. It is unclear whether the development of disease is related to a single injury or rather multiple insults over time, but studies have reported the development of Dupuytren's near the site of previous penetrating injuries [27]. Other studies have linked previous hand surgery such as carpal tunnel and trigger finger release to the development of Dupuytren's disease [22, 25, 28, 29].

#### *3.3.5. Other risk factors*

The association between Dupuytren's disease and epilepsy or anticonvulsants and has been reported. Lund et al. recorded a 50% prevalence of Dupuytren's in male patients with epilepsy and 25% in females [30]. Another study identified an overall prevalence of Dupuytren's disease in 37% of epileptics [31]. Critchley et al. reported a 56% incidence of Dupuytren's disease in chronic epileptic patients and an associated increased in disease with duration of epilepsy and possibly related to the administration of the anticonvulsant phenobarbital [32]. The effect of phenobarbital on DD was analyzed in a 2011 study, in which a dose-dependent fibrotic effect was seen with phenobarbital use. Though these studies demonstrate a relationship between epilepsy and phenobarbital use in DD, other studies have found no direct correlation to antiepileptic drugs [33, 34].

Manuel labor consisting of continued and repetitive hand use has also been proposed as a risk factor for developing Dupuytren's disease. Lucas et al. reported the effect of personal and occupation exposures on the development of the disease and reported men who developed the disease had the highest exposure to biomechanical, vibration, and manual work [35]. After adjusting for personal risk factors, manual labor and the handling of vibratory tools had the strongest association with Dupuytren's disease. Another study examining the effect of weekly hand transmitted vibration on the development of Dupuytren's disease concluded the risk of developing Dupuytren's contracture is more than double in men with increasing amounts of hand-transmitted vibration [34]. In addition, handwork for at least 30 years has also been reported as a possible risk factor in the development of Dupuytren's disease [35].
